Entamoeba histolytica: Purification and characterization of ornithine decarboxylase
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Ornithine decarboxylase, a rate-limiting enzyme in polyamine biosynthesis in eukaryotes, was stabilized and purified from trophozoites of the parasite protozoan E. histolytica. Analytical electrophoresis revealed the presence in the purified preparations of a major polypeptide of 45kDa and barely detectable amounts of two other proteins of 70 and 120kDa. Both the 45 and 70kDa polypeptides were recognized by a mouse anti-ODC monoclonal antibody. The major polypeptide exhibited amino terminal sequence homology in the range of 40-73%25 with ODCs from other organisms. The immunoreactive polypeptide of 70kDa was not identified. The molecular masses of 216 and 45kDa determined for the native enzyme by gel filtration and for the major polypeptide by SDS-PAGE, respectively, suggest that the amoeba ODC is a homopentamer. Dialysis against hydroxylamine rendered the enzyme activity fully dependent on pyridoxal 5′-phosphate (PLP). As expected for an oligomeric enzyme, ODC activity exhibited sigmoidal kinetics when it was measured as a function of increasing concentrations of L-ornithine and PLP yielding S0.5 values of 0.45 and 0.18mM, respectively. Purified ODC was inhibited by 1,3-diaminopropane and 2,4-diamino-2-butanone but was largely insensitive to inhibition by α-difluoromethylornithine (DFMO), indicating that the enzyme may not be a suitable target for this anti-parasitic drug. Other features of the amoeba ODC were common with the enzyme from prokaryotes and eucaryotes. © 2003 Elsevier Science (USA). All rights reserved.
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1,3 propanediamine; 2 butanone; 2,4 diamino 2 butanone; eflornithine; hydroxylamine; monoclonal antibody; ornithine; ornithine decarboxylase; polypeptide; pyridoxal 5 phosphate; unclassified drug; amino terminal sequence; article; controlled study; dialysis; Entamoeba histolytica; enzyme activity; enzyme inhibition; enzyme purification; enzyme stability; eukaryote; gel filtration; molecular weight; nonhuman; polyacrylamide gel electrophoresis; priority journal; prokaryote; sequence homology; Entamoeba; Entamoeba histolytica; Eukaryota; Prokaryota; Protozoa
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